One RSV shot cuts severe lung infections in older adults for three seasons, trial shows

By Dr. Liji Thomas, MDApr 23 2025

A landmark global trial shows that one dose of the RSVPreF3 OA vaccine protects older adults against serious RSV lung disease for three seasons, raising hopes for long-term protection with just a single shot.

Study: Efficacy, safety, and immunogenicity of the AS01_E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial. Image Credit: CI Photos / Shutterstock

Respiratory syncytial virus (RSV) vaccines were rolled out in 2023, including the AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA). A recent study in The Lancet Respiratory Medicine explored the duration of protection against lower respiratory tract disease caused by RSV (RSV-LRTD) following administration of RSVPreF3 OA.

Introduction

RSV causes seasonal outbreaks of respiratory disease, particularly among adults over 60 years of age. This risk is exacerbated in the presence of chronic illnesses like chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF), or metabolic conditions like diabetes or kidney failure.

RSV vaccines have been a research goal for over six decades. Currently, three approved vaccines against this virus are available: the adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA), the bivalent RSV prefusion F protein-based vaccine (RSVPreF), and the RSV prefusion F mRNA-based vaccine (mRNA-1345). Each appears effective in protecting against symptomatic RSV-LRTD for at least one season. However, the actual protection duration and the best revaccination timing remain open questions.

Study Findings

The current study employed a randomized, placebo-controlled, observer-blinded Phase 3 trial design to evaluate the duration of protection provided by this vaccine. The study included 24,972 participants aged 60 years or older from 17 countries and 275 centers. The average age was 69.5 years.

Participants were randomized to receive either RSVPreF3 OA or placebo prior to the first RSV seasonal outbreak (season 1). Vaccine recipients were further randomized to receive either a second dose of the vaccine (revaccination group) or a placebo (single-dose group) before the second RSV season (Season 2). All those who received a placebo before season 1 got a second placebo dose before season 2.

After a median follow-up of 30.6 months, a single dose of RSVPreF3 OA reduced symptomatic RSV-LRTD by 62.9% (97.5% CI 46.7–74.8) over three RSV seasons. The vaccine protected against the spectrum of RSV-LRTD, including a 51.1% reduction in RSV-related acute respiratory illness (95% CI 40.3–60.2), a 67.4% reduction in severe RSV-LRTD (95% CI 42.4–82.7), and a 70.2% reduction in cases requiring medical attention (95% CI 50.1–83.1).

Age-Specific and Strain-Specific Efficacy

Age-specific efficacy varied slightly, with 60.3% (95% CI 39.5–74.8) protection in adults aged 60–69 and 70.6% (95% CI 48.4–84.3) in those aged 70–79. However, efficacy could not be reliably estimated in frail adults (walking speed <0.4 m/s) or those aged 80 years or older due to the small case numbers.

Strain-specific efficacy was 69.8% against RSV A-LRTD (97.5% CI 42.2–85.7) and 58.6% against RSV B-LRTD (97.5% CI 35.9–74.1), critical given annual variability in circulating subtypes.

Waning Immunity and Revaccination

Waning immunity was observed, with efficacy declining from 82.6% in Season 1 to 56.1% in Season 2 and 48.0% in Season 3. Neutralizing antibody titers remained above baseline for three seasons but decreased most sharply after the first year.

Revaccination with a second dose (revaccination group) showed 67.8% cumulative efficacy (97.5% CI 51.8–79.1), within the same range as a single dose, though the trial was not designed to statistically compare regimens.

Safety

Safety data revealed that fewer than 1% of participants in both the vaccine and placebo groups reported serious adverse events deemed related to the intervention. Five deaths were assessed as vaccine-related (3 vaccine, 2 placebo), though all had pre-existing conditions or occurred long after vaccination.

Conclusions

This is the first Phase 3 trial to demonstrate the three-season efficacy of a licensed RSV vaccine in older adults. While protection waned over time, a single dose maintained 48% efficacy in season 3. Revaccination after one year did not significantly boost efficacy in the overall population, though low case numbers limited subgroup analyses (e.g., by frailty).

The study measured protection against symptomatic lower respiratory tract disease (LRTD), not all RSV infections. Hospitalizations were rare, with only 8 total cases, preventing the drawing of robust conclusions about severe outcomes.

The findings support RSVPreF3 OA’s favorable benefit-risk profile over three seasons; however, further research is needed to optimize revaccination timing, particularly for high-risk subgroups, such as frail adults or those aged 80 years or older.